Custom-synthesized, oligonucleotide probes have emerged as a powerful tool for the identification and isolation of specific nucleic acid targets via hybridization. Applications for such hybridization probe sets range from next generation sequencing—where such probes are used to enrich or deplete samples for specific nucleic acid targets—to imaging of fixed samples—where fluorescently labeled hybridization probes allow the direct measurement of the number and spatial organization of the targeted species.
There are now a wide range of commercial sources for such probes. Such probes are often made by synthesizing each oligonucleotide member using standard solid phase synthesis methods. Unfortunately, this limits both the number of probes within a single set and the number of unique sets, due to the requirement that each oligonucleotide member must be individually and separately synthesized.
Recent advances in array-based synthesis of oligonucleotides by several companies have reduced the cost of producing oligonucleotides. However, these approaches also result in 1000-fold less oligonucleotide probes than is required for a single hybridization reaction, thus limiting their usefulness. Accordingly, improvements in oligonucleotide production are needed.